The treatment of chronic pain is difficult and often unsuccessful. Opiate analgesics have the unwanted side effect of producing tolerance and dependence. the recent use of electrical stimulation of discrete loci in the brain has created a new and possibly very useful treatment for intractable pain. The proposed experiments examine whether SPA is mediated by the endogenous opiate system, and if so, whether an opiate-like dependence can be elicited with repetitive stimulation. All rats will be implanted with one or more bipolar electrodes in the medial brainstem area. Rats will be tested for pain sensitivity by sue of a tail-flick test to noxious radiant heat stimulation. They will also be observed for abstinence signs associated with opiate withdrawal. The first study will examine the extent of system activation with stimulation-produced analgesia (SPA). Repeated electrical stimulation will be delivered at one electrode site until tolerance to the behavioral effect is observed. Another locus, which has not been given repeated stimulation, will then be stumulated to determine whether SPA tolerance spreads beyond the electrode locus. In Experiment II rats will receive repetitive bursts of electrical stimulation in one or more brain areas previously reported to elicit SPA. Upon termination of stimulation, rats will be observed for opiate withdrawal signs before and after IP administration of 5 mg/kg naloxone hydrochloride. In the third experiment, rats will be implanted with pellets containing 75 mg morphine sulfate. After dependence is established (72 hrs.) the pellet will be removed and rats will be observed for opiate abstinence signs. Animals will then receive repetitive bursts of electrical stimulation in one or more areas previously reported to elicit SPA. They will again be observed for opiate abstinence, to determine if SPA attenuates withdrawal signs in an opiate dependent rat. Results of the above studies will clarify the phenomenon of tolerance to analgesic electrical brain stimulation, and will provide information regarding the possibility for dependence upon such stimulation. Future experiments with an appropriate human population are planned.